Highlights
- •All SCCOHT patients should undergo genetic testing for germline SMARCA4 mutations.
- •HDC-aSCR may offer SCCOHT patients the best outcome, and should be studied further.
Abstract
Objective
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor,
with long term survival at ~30% in early stage disease. SCCOHT is caused by germline and somatic SMARCA4 mutations, but the effect of the mutation type on patients remains unknown. Furthermore,
the rarity of SCCOHT has resulted in varied treatment, with no standardized protocols.
We analyzed 293 cases to determine the effect of treatment modalities and SMARCA4 mutations on patient diagnosis and outcome.
Methods
In 293 SCCOHT patients we collected information on age and stage at diagnosis, treatment
modality (surgery, chemotherapy, radiotherapy, and/or high-dose chemotherapy with
autologous stem cell rescue (HDC-aSCR)), SMARCA4 mutation origin (germline/somatic), and overall survival. Cox analysis and log-rank
tests were performed on 257 cases with available survival data.
Results
The strongest prognostic factors were stage at diagnosis (p = 2.72e‐15) and treatment modality (p = 3.87e‐13). For FIGO stages II–IV, 5-year survival was 71% for patients who received
HDC-aSCR, compared to 25% in patients who received conventional chemotherapy alone
following surgery (p = 0.002). Patients aged ≥40 had a worse outcome than younger patients (p = 0.04). Twenty-six of 60 tested patients carried a germline SMARCA4 mutation, including all patients diagnosed <15 years; carriers presented at a younger age than non-carriers (p = 0.02).
Conclusions
Stage at diagnosis is the most significant prognostic factor in SCCOHT and consolidation
with HDC-aSCR may provide the best opportunity for long-term survival. The large fraction
of SMARCA4 germline mutations carriers warrants genetic counseling for all patients.
Keywords
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Article info
Publication history
Published online: March 11, 2016
Accepted:
March 10,
2016
Received in revised form:
March 9,
2016
Received:
January 30,
2016
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
